This is a revised renewal application for the study of the neuroendocrinology of severe depression, including anterior pituitary hormone secretion patterns, their regulation of peripheral steroid hormones, and the integrity of their control mechanisms as reflected by responses to perturbation tests including thyrotropin releasing hormone, luteinizing hormone releasing hormone, and dexamethasone suppression. Both male and female endogenously depressed patients are being studied under a three-day protocol with frequent blood sampling being done for the elucidation of multiple hormone secretion patterns. Patients are studied after one week of hospitalization before any treatment, after one month of tricyclic antidepressant medication of ECT, and several months following discontinuation of treatment. Psychological ratings for degree of depression are performed at each stage of the patients' illnesses. It is also planned to measure levels of CSF monoamines and their metabolites before treatment, in collaboration with the Stanford MHCRC. Additional work will include continued collaboration with Dr. B. Carroll in the physostigmine-induced cortisol escape from dexamethasone suppression, which is a pharmacologic model of this escape phenomenon in depression; the continued improvement of radioimmunoassay techniques for hormone measurement; and attempting to develop a radioimmunoassay for MHPG.